Herdiansyah, Mochammad Aqilah and Darmanto, Win and Winarni, Dwi and Rohmatika, Aulia Umi and Putri, Rr Aulia Rahmawati Kusuma and Susilo, Raden Joko Kuncoroningrat and Sucipto, Teguh Hari and Wiradana, Putu Angga and Khanifah, Farach and Ernawati, Ernawati (2026) Decoding antidengue serotype-3 (DENV-3) mechanism of natural glycosides from Alpinia purpurata: Molecular docking and in vitro insights into viral entry, cytokine storm modulation, and endogenous antioxidant defense activation. Open Veterinary Journal, 16 (5). 2987 - 3007. ISSN 22264485

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Abstract

Background: Dengue virus serotype-3 (DENV-3) infection remains a clinical problem for which no specific antiviral agent has yet been identified. The rhizome of Alpinia purpurata (red galangal) is rich in natural glycosides with antioxidant and anti-inflammatory properties. However, studies related to antidengue from A. purpurata using in vitro and in silico methods have not been widely conducted. Aim: This study aims to describe the anti-dengue mechanism of natural glycosides from A. purpurata rhizomes through their antiviral ability in vitro in Vero E6 cell cultures induced by DENV-3 and molecular docking to the DC-SIGN (CD209), CD300a, IL-1β, and SOD receptors. Methods: In vitro quantification of the viral replication inhibition value was performed using dengue virus antibodies (4G2) through ELISA. Meanwhile, molecular docking was performed to assess the binding affinities and complex interactions. Molecular dynamics simulations confirmed the stability of the docking complexes within the root mean square fluctuation value. Further screening was conducted using the pkCSM webserver to obtain the ADMET property values and the ProTox 3.0 webserver to obtain the toxicity prediction values. Results: In vitro DENV-3-induced Vero E6 cell cultures induced with DENV-3 showed a viral replication inhibition value of 105.8107 µg/mL. Molecular docking experiments revealed that quercetin-3-O-rutinoside has the best potential to inhibit virus binding to DC-SIGN receptors (â7.8 kcal/mol), balance immune signals through CD300a regulation (â7.1 kcal/mol), suppress the production of IL-1β during cytokine storm (â7.2 kcal/mol), and activate endogenous antioxidant superoxide dismutase (â7.0 kcal/mol) compared with quercetin control. The validation of docking results through molecular dynamics proved that the quercetin-3-O-rutinoside complex has an RMSF value < 3 à , which means that the complex tends to be stable. ADMET characteristics and toxicity also indicate that quercetin-3-O-rutinoside is safe for cells. Conclusion: This study reports the first evidence of the potential of natural glycosides from A. purpurata as antidengue agents in vitro and in silico through viral entry inhibition, cytokine storm modulation, and endogenous antioxidant activation to reduce free radicals in cells during infection. These findings support the potential of A. purpurata as an antiviral, anti-inflammatory, and antioxidant agent. © 2026, Faculty of Veterinary Medicine, University of Tripoli. All rights reserved.

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